Significance The maintenance of long-term immunologic memory is the hallmark of a successful viral vaccine, and any novel measles vaccine will be evaluated in monkeys for its ability to generate and maintain memory. Objectives This proposal is designed to use the nonhuman primate model of measles pathogenesis to address issues basic to new measles vaccine development. There are two specific aims to measure the strength and duration of vaccine-induced immune responses to measles virus, and to correlate immunologic memory and viral persistence. Does measles virus persist as viral antigen or viral RNA in tissues ? Results Rhesus monkeys infected with measles virus can develop a clinical syndrome similar to that in humans, and they acquire resistance to re-infection. We have established an experimental model of pathogenic measles infection of rhesus monkeys. After intranasal inoculation of measles virus, rhesus monkeys develop skin rash, bronchitis, interstitial pneumonia and acute inflammation in lymph nodes, spleen and the thymus. Attenuated measles vaccine prevents systemic infection and/or disease in rhesus monkeys. Correlates of protective immunity in naive or measles-vaccinated juvenile monkeys include neutralizing antibody and cytotoxic T cell responses to measles virus. These responses have been detected up to 1 year after vaccination or after infection with the pathogenic virus. Future Dirtections Recently, we have detected persistence of viral RNA in the tissues of monkeys at more than 1 year after the acute infection. Future studies will characterize the nature of viral persistence and its relationship to the maintenance of immunologic memory to measles virus. KEYWORDS measles, protective immunity, vaccine